Monoamine oxidase (MAO), a major intracellular enzyme which degrades biogenic amines in mammalian brain, has been proposed to play a role in a variety of psychiatric and neurological disorders involving oatecholamine abnormalities, including schizophrenia, affective disorders, and Parkinson's disease. Clinical studies of MAO have focused almost exclusively on platelet MAO (MAO B) because of its accessibility; of the few studies which have analyzed MAO activity in the human brain, only regional comparisons of homogenized tissue have been attempted. Using new reagents developed in our laboratories, we propose to undertake the first comprehensive study of the regional and cellular localization of MAO A and B in monkey and human autopsy brain by immunoperoxidase staining with our MAO A- and B-specific monoclonal antibodies. We will also identify MAO-rich cell types and brain regions of importance to Parkinson's disease by co-staining for serotonin, dopamine-beta-hydroxylase, phenylethanolamine-N-methyltransferase, tyrosine hydroxylase, dihydropteridine reductase, and glial fibrillary acidic protein. MAO in localized in regions will be subjected to computer-quantitated immunohistochemical analysis in stained, fixed tissue, and radioenzymatic activity assays and radioimmunoassays of enzyme concentration in extracts of tissue preserved by freezing. Electron microscopy will be used to determine the orientation of MAO in the inner and outer surfaces of the outer mitochondrial membrane. After initial studies in whole monkey and normal human brains are complete, we will begin studies comparing MPTP-treated and untreated monkey brain, and parallel studies in humans of autopsy brain tissues from patients diagnosed as having Parkinson's disease and age- and sex-matched normal controls. The monkey experiments will help us evaluate possible effects of L-dopa on MAO distribution in Parkinson's patients treated with that drug. The Parkinson's studies should allow us to validate our new methodologies in a disease with well documented anatomical and biochemical abnormalities in specific neural tracts; they may also reveal important new information about the roles of MAO A and B in this disorder. We and others have recently found that MAO oxidizes the neurotoxin MPTP to an active metabolite(s) in a sequence of moleclar events that induce Parkinson's disease in humans and monkeys. Localizing MAO A and B in the brain should increase our understanding of the physiological roles of these two important amine metabolizing enzymes.